Safety/Listeriolysin and Invasin
What are Listeriolysin and Invasin?
Listeriolysin O (LLO) is a protein from the bacterium Listeria monocytogenes, which is a [http://2014.igem.org/Safety/Risk_Group_Guide Risk Group 2] human pathogen. LLO is a virulence factor, because it helps Listeria infect human cells. Specifically, once the Listeria have been taken up into vesicles in the cytoplasm of a human cell, the LLO protein breaks open the vesicle membrane, releasing Listeria into the host cell cytoplasm.
Invasin is a protein from the bacterium Yersinia pestis (Peste or Black Plague), which is a [http://2014.igem.org/Safety/Risk_Group_Guide Risk Group 3] human pathogen. (Variants of the Invasin protein are found in closely related bacteria, such as Yersinia enterocolitica, which are Risk Group 2 pathogens.) Invasin is also a virulence factor. Invasin helps Y. pestis invade human cells.
What safety risks are associated with these parts?
Both Listeriolysin and Invasin present a moderate amount of danger by themselves, because each part helps foreign bacteria get one step closer to living inside human cells. However, they are most dangerous when they are combined together. Genetically engineered bacteria that express both Listeriolysin and Invasin are able to invade human cells and penetrate to the cytoplasm at high efficiencies. This effectively hides them from the immune system, so they can live and work inside the human cytoplasm without being stopped by immune cells.
While this invading ability is often very useful for a synthetic system, it is also an extremely dangerous ability for engineered cells to have. If engineered cells can hide from the human immune system and continue to grow and thrive, then their ability to cause disease is much, much greater. Granting this ability to an innocuous germ might turn it into a pathogen. Granting this ability to a moderately dangerous pathogen might turn it into an extremely dangerous one.
iGEM does not ban the use of Listeriolysin or Invasin, whether alone or together. However, if any participants wish to work with these parts, we require that they observe strict safety procedures. [http://2014.igem.org/Safety_Hub#rgbsl Biosafety Level 2 containment] is appropriate for projects that incorporate Listeriolysin and Invasin.
For the 2014 competition, teams must complete a [http://2014.igem.org/Safety/Check_In Check-In form] and receive approval before acquiring or using Listeriolysin or Invasin.